• Title/Summary/Keyword: SH3 domain

Search Result 61, Processing Time 0.028 seconds

Differential Gene Expression in Estradiol-3-Benzoate-Treated Liver and Chemically- Induced Hepatocellular Carcinoma

  • KIM , SEYL;KANG, JIN-SEOK;JANG, DONG-DEUK;LEE, KOOK-KYUNG;KIM, SOON-AE;HAN, BEOM-SEOK;PARK, YOUNG-IN
    • Journal of Microbiology and Biotechnology
    • /
    • v.14 no.6
    • /
    • pp.1286-1294
    • /
    • 2004
  • In a previous study by the current authors, hepatocellular carcinoma (HCC) was determined to be epidemiologically sex-dependent, and the incidence and multiplicity of HCC found to decrease in estradiol-3 benzoate (EB)-treated F344 rats. Therefore, to ascertain the anticancer mechanism of EB, a commercially available cDNA microarray, with a total of 14,815 cDNA rat gene clones, was used to determine the differentially expressed genes in nontreated livers, EB-treated livers, and diethynitrosolamine (DEN)-induced HCC. In the sequenced experiment, a total of 85 genes were differentially expressed at either two or more times the rate of the normal expression, where 33 genes were downregulated by EB, and 52 genes upregulated. Candidate genes were selected according to significant changes observed in the mRNA expression in the EB-treated livers compared with the nontreated livers, then these genes were filtered according to their different expression patterns in the DEN-induced tumors compared to the estrogen-treated livers. To confirm the microarray data, a real-time PCR analysis was performed for ten selected genes: the H-ras revertant protein 107 (H­rev107), insulin-like growth factor binding protein (lOFBP), parathyroid hormone receptor (PI'HR), SH3 domain binding protein (SH3BP), metallothionein, src-suppressed C-kinase substrate (SSeCK) gene, phosphodiesterase I, CD44, epithelial membrane protein 3 (EMP3), and estrogen receptor a (ERa). The SSeCK and phosphodiesterase I genes were both upregulated in the DEN-induced hepatocarcinomas, yet their possible carcinogenic functions remain unknown. Meanwhile, the other genes were downregulated, including the genes related to growth regulation (IOFBP, H-revI07, ER$\alpha$), adipogenesis inhibition (PTHR), and tumor suppression (metallothionein).

Seismic Response Analysis for Three Dimensional Soil-structure Interaction System using Dynamic Infinite Elements (동적 무한요소를 이용한3차원 지반-구조물 상호작용계의 지진응답해석)

  • Seo, Choon-Gyo;Ryu, Jeong-Soo;Kim, Jae-Min
    • Journal of the Earthquake Engineering Society of Korea
    • /
    • v.12 no.6
    • /
    • pp.55-63
    • /
    • 2008
  • This paper presents a seismic analysis technique for a 3D soil-structure interaction system in a frequency domain, based on the finite element formulation incorporating frequency-dependent infinite elements for the far field soil region. Earthquake input motions are regarded as traveling P, SV and SH waves which are incident vertically from the far-field soil region, and then equivalent earthquake forces are calculated using impedances of infinite soil by dynamic infinite elements and traction and displacement from free field response analysis. For verification and application, seismic response analyses are carried out for a multi-layered soil medium without structure and a typical nuclear power plant in consideration of soil-structure interaction. The results are compared with the free field response using a one-dimensional analytic solution, and a dynamic response of an example structure from another SSI package.

Discrimination of Local Microearthquakes and Artificial Underground Explosions on the Basis of Time-Frequency Domain (시간-주파수 영역에서의 국지 미소지진과 지하인공폭발의 구별)

  • 김소구;박용철
    • The Journal of Engineering Geology
    • /
    • v.7 no.1
    • /
    • pp.63-79
    • /
    • 1997
  • In this study, our purpose is to develop a technique to discriminate artificial explosions from local microearthquakes on the basis of time-frequency domain. To obtain spectral features of artificial explosions and microearthquakes, we used 3-d spectrograms(frequency, time and amplitude) because this is a useful tool to study the frequency content of entire seismic waveforms observed at local and regional distances (e. g., Kim et al., 1994). P and S waves from quarry blasts show that frequency content of dominant amplitude appeared above 10 Hz and Rg phases that are observed at near distance ranges. But P and S waves from microearthquakes have more broad frequency content as well as below 10 Hz. And for discrimination, Pg/Lg spectral ratio is performed below 10 Hz. In order to select time windows we computed group velocity using multiple filter method(MFM) and removed free surface effects from all 3-components data for improving on data quality. Next step, we computed Fast-Fourier transform, and a log average spectral amplitude over seven frequency bands : 0.5 to 3, 2 to 4, 3 to 5, 4 to 6, 5 to 7, 6 to 8 and 8 to 10 Hz. The best separation is observed from 6 to 8 Hz.

  • PDF

Expression of Phospholipase C Isozymes in Human Lung Cancer Tissues (인체 폐암조직에서 Phospholipase C 동위효소의 발현양상)

  • Hwang, Sung-Chul;Mah, Kyung-Ae;Choi, So-Yeon;Oh, Yoon-Jung;Choi, Young-In;Kim, Deog-Ki;Lee, Hyung-Noh;Choi, Young-Hwa;Park, Kwang-Ju;Lee, Yi-Hyeong;Lee, Kyi-Beom;Ha, Mahn-Joon;Bae, Yoon-Su
    • Tuberculosis and Respiratory Diseases
    • /
    • v.49 no.3
    • /
    • pp.310-322
    • /
    • 2000
  • Background : Phospholipase C(PLC) plays an important role in cellular signal transduction and is thought to be critical in cellular growth, differentiation and transformation of certain malignancies. Two second messengers produced from the enzymatic action of PLC are diacylglycerol (DAG) and inositol 1, 4, 5-trisphosphate (IP3). These two second messengers are important in down stream signal activation of protein kinase C and intracellular calcium elevation. In addition, functional domains of the PLC isozymes, such as Src homology 2 (SH2) domain, Src homology 3 (SH3) domain, and pleckstrin homology (PH) domain play crucial roles in protein translocation, lipid membrane modificailon and intracellular memrane trafficking which occur during various mitogenic processes. We have previously reported the presence of PLC-${\gamma}1$, ${\gamma}2$, ${\beta}1$, ${\beta}3$, and ${\delta}1$ isozymes in normal human lung tissue and tyrosine-kinase-independent activation of phospholipase C-${\gamma}$ isozymes by tau protein and AHNAK. We had also found that the expression of AHNAK protein was markedly increased in various mstologic types of lung can∞r tissues as compared to the normallungs. However, the report concerning expression of various PLC isozymes in lung canærs and other lung diseases is lacking. Therefore, in this study we examined the expression of PLC isozymes in the paired surgical specimens taken from lung cancer patients. Methods : Surgically resected lung cancer tissue samples taken from thirty seven patients and their paired normal control lungs from the same patients, The expression of various PLC isozymes were studied. Western blot analysis of the tissue extracts for the PLC isozymes and immunohistochemistry was performed on typical samples for localization of the isozyme. Results : In 16 of 18 squamous cell carcinomas, the expression of PLC-${\gamma}1$ was increased. PLC-${\gamma}1$ was also found to be increased in all of 15 adenocarcinoma patients. In most of the non-small cell lung cancer tissues we had examined, expression of PLC-${\delta}1$ was decreased. However, the expression of PLC-${\delta}1$ was markedly increased in 3 adenocarcinomas and 3 squamous carcinomas. Although the numbers were small, in all 4 cases of small cell lung cancer tissues, the expression of PLC-${\delta}1$ was nearly absent. Conclusion : We found increased expression of PLC-${\gamma}1$ isozyme in lung cancer tissues. Results of this study, taken together with our earlier findings of AHNAK protein-a putative PLD-${\gamma}$, activator-over-expression, and the changes observed in PLC-${\delta}1$ in primary human lung cancers may provide a possible insight into the derranged calcium-inositol signaling pathways leading to the lung malignancies.

  • PDF

Directional adjacency-score function for protein fold recognition

  • Heo, Mu-Young;Cheon, Moo-Kyung;Kim, Suhk-Mann;Chung, Kwang-Hoon;Chang, Ik-Soo
    • Interdisciplinary Bio Central
    • /
    • v.1 no.2
    • /
    • pp.8.1-8.6
    • /
    • 2009
  • Introduction: It is a challenge to design a protein score function which stabilizes the native structures of many proteins simultaneously. The coarse-grained description of proteins to construct the pairwise-contact score function usually ignores the backbone directionality of protein structures. We propose a new two-body score function which stabilizes all native states of 1,006 proteins simultaneously. This two-body score function differs from the usual pairwise-contact functions in that it considers two adjacent amino acids at two ends of each peptide bond with the backbone directionality from the N-terminal to the C-terminal. The score is a corresponding propensity for a directional alignment of two adjacent amino acids with their local environments. Results and Discussion: We show that the construction of a directional adjacency-score function was achieved using 1,006 training proteins with the sequence homology less than 30%, which include all representatives of different protein classes. After parameterizing the local environments of amino acids into 9 categories depending on three secondary structures and three kinds of hydrophobicity of amino acids, the 32,400 adjacency-scores of amino acids could be determined by the perceptron learning and the protein threading. These could stabilize simultaneously all native folds of 1,006 training proteins. When these parameters are tested on the new distinct 382 proteins with the sequence homology less than 90%, 371 (97.1%) proteins could recognize their native folds. We also showed using these parameters that the retro sequence of the SH3 domain, the B domain of Staphylococcal protein A, and the B1 domain of Streptococcal protein G could not be stabilized to fold, which agrees with the experimental evidence.

Seismic motions in a non-homogeneous soil deposit with tunnels by a hybrid computational technique

  • Manolis, G.D.;Makra, Konstantia;Dineva, Petia S.;Rangelov, Tsviatko V.
    • Earthquakes and Structures
    • /
    • v.5 no.2
    • /
    • pp.161-205
    • /
    • 2013
  • We study seismically induced, anti-plane strain wave motion in a non-homogeneous geological region containing tunnels. Two different scenarios are considered: (a) The first models two tunnels in a finite geological region embedded within a laterally inhomogeneous, layered geological profile containing a seismic source. For this case, labelled as the first boundary-value problem (BVP 1), an efficient hybrid technique comprising the finite difference method (FDM) and the boundary element method (BEM) is developed and applied. Since the later method is based on the frequency-dependent fundamental solution of elastodynamics, the hybrid technique is defined in the frequency domain. Then, an inverse fast Fourier transformation (FFT) is used to recover time histories; (b) The second models a finite region with two tunnels, is embedded in a homogeneous half-plane, and is subjected to incident, time-harmonic SH-waves. This case, labelled as the second boundary-value problem (BVP 2), considers complex soil properties such as anisotropy, continuous inhomogeneity and poroelasticity. The computational approach is now the BEM alone, since solution of the surrounding half plane by the FDM is unnecessary. In sum, the hybrid FDM-BEM technique is able to quantify dependence of the signals that develop at the free surface to the following key parameters: seismic source properties and heterogeneous structure of the wave path (the FDM component) and near-surface geological deposits containing discontinuities in the form of tunnels (the BEM component). Finally, the hybrid technique is used for evaluating the seismic wave field that develops within a key geological cross-section of the Metro construction project in Thessaloniki, Greece, which includes the important Roman-era historical monument of Rotunda dating from the 3rd century A.D.

Improvement of inspection system for common crossings by track side monitoring and prognostics

  • Sysyn, Mykola;Nabochenko, Olga;Kovalchuk, Vitalii;Gruen, Dimitri;Pentsak, Andriy
    • Structural Monitoring and Maintenance
    • /
    • v.6 no.3
    • /
    • pp.219-235
    • /
    • 2019
  • Scheduled inspections of common crossings are one of the main cost drivers of railway maintenance. Prognostics and health management (PHM) approach and modern monitoring means offer many possibilities in the optimization of inspections and maintenance. The present paper deals with data driven prognosis of the common crossing remaining useful life (RUL) that is based on an inertial monitoring system. The problem of scheduled inspections system for common crossings is outlined and analysed. The proposed analysis of inertial signals with the maximal overlap discrete wavelet packet transform (MODWPT) and Shannon entropy (SE) estimates enable to extract the spectral features. The relevant features for the acceleration components are selected with application of Lasso (Least absolute shrinkage and selection operator) regularization. The features are fused with time domain information about the longitudinal position of wheels impact and train velocities by multivariate regression. The fused structural health (SH) indicator has a significant correlation to the lifetime of crossing. The RUL prognosis is performed on the linear degradation stochastic model with recursive Bayesian update. Prognosis testing metrics show the promising results for common crossing inspection scheduling improvement.

PEP-1-HO-1 prevents MPTP-induced degeneration of dopaminergic neurons in a Parkinson's disease mouse model

  • Youn, Jong Kyu;Kim, Dae Won;Kim, Seung Tae;Park, Sung Yeon;Yeo, Eun Ji;Choi, Yeon Joo;Lee, Hae-Ran;Kim, Duk-Soo;Cho, Sung-Woo;Han, Kyu Hyung;Park, Jinseu;Eum, Won Sik;Hwang, Hyun Sook;Choi, Soo Young
    • BMB Reports
    • /
    • v.47 no.10
    • /
    • pp.569-574
    • /
    • 2014
  • Heme oxygenase-1 (HO-1) degrades heme to carbon dioxide, biliverdin, and $Fe^{2+}$, which play important roles in various biochemical processes. In this study, we examined the protective function of HO-1 against oxidative stress in SH-SY5Y cells and in a Parkinson's disease mouse model. Western blot and fluorescence microscopy analysis demonstrated that PEP-1-HO-1, fused with a PEP-1 peptide can cross the cellular membranes of human neuroblastoma SH-SY5Y cells. In addition, the transduced PEP-1-HO-1 inhibited generation of reactive oxygen species (ROS) and cell death caused by 1-methyl-4-phenylpyridinium ion ($MPP^+$). In contrast, HO-1, which has no ability to transduce into SH-SY5Y cells, failed to reduce $MPP^+$-induced cellular toxicity and ROS production. Furthermore, intraperitoneal injected PEP-1-HO-1 crossed the blood-brain barrier in mouse brains. In a PD mouse model, PEP-1-HO-1 significantly protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity and dopaminergic neuronal death. Therefore, PEP-1-HO-1 could be a useful agent in treating oxidative stress induced ailments including PD.

Overview on Molecular Toxicological Aspects of Helicobacter pylori Virulence Factor, Cytotoxin-associated Antigen A (CagA) (헬리코박터 파이로리의 병원성 단백질, CagA에 대한 분자 독성학적 측면에서의 고찰)

  • Kim Byung J.;Jung Hwa Jin;Hwang Jee Na;Kang Seok Ha;Oh Se-Jin;Seo Young Rok
    • Toxicological Research
    • /
    • v.20 no.3
    • /
    • pp.179-185
    • /
    • 2004
  • Helicobacter pylori (H. pylori) infects more than half of the people in the world as a major microbe to cause most of gastric diseases. Recently, cytotoxin associated-antigen A (CagA) is believed as one of the most important virulence factors of H. pylori. Molecular toxicological pathway of CagA is necessary to investigate for understanding the pathological and toxicological aspects of H. pylori, since this virulence protein harasses intercellular processes of host cells to get profit for the survival of H. pylori. CagA is coded from cag pathogenicity island (cag PAI) and translocated into host cells by Type 4 secretion system (TFSS). Tyrosine phosphorylation of CagA targets Src homology 2-containing phosphotyrosine phosphatase (SHP-2) to form a CagA-SHP-2 complex. This complex depends on the similarity of sequence between EPIYA motif and Src homology 2 domain (SH2 domain) of CagA. The generation of growth factors is an essential role of CagA in protecting and healing gastric mucosa for the survival of H. pylori. On the other hand, the activation of IL-8 by CagA induces neutrophils generating inflammation and free radicals. Indeed, free radicals are well known carcinogen to induce DNA damage. In addition, the transduction of mitogen-activation signal by CagA is one of the interesting features to understand how to cause cancer. The relationship between cancer and inflammation with CagA was mainly discussed in this review.

DOBI is cleaved by caspases during TRAIL-induced apoptotic cell death

  • Park, Sun-Young;Shin, Jin-Na;Woo, Ha-Na;Piya, Su-Jan;Moon, Ae-Ran;Seo, Young-Woo;Seol, Dai-Wu;Kim, Tae-Hyoung
    • BMB Reports
    • /
    • v.42 no.8
    • /
    • pp.511-515
    • /
    • 2009
  • Downstream of Bid (DOBI) known as Pus10, has been identified as a modulator of TRAIL-induced cell death using RNAi library screening. The crystal structure of DOBI has revealed that it is a crescent-shaped protein containing the pseudouridine synthase catalytic domain and a THUMP-containing domain. Here, we demonstrated that DOBI is expressed in various tissues such as heart and lung, and is also expressed in various tumor cells such as HeLa and A549. Although ectopic expression of DOBI does not promote TRAIL death signaling in HeLa cells, knock-down of DOBI expression using shRNA inhibited TRAIL death signaling. DOBI is cleaved into a 54 kD cleaved DOBI during cell death, and the recombinant DOBI protein can be directly cleaved by caspases-3, or -8 in vitro. Together, these data suggest that the cleaved DOBI may acquire a new function, possibly by cooperating with tBid in the mitochondrial event of cell death caused by TRAIL.